The targeted delivery of doxorubicin with transferrin-conjugated block copolypeptide vesicles

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• 作者：Brian S. Lee ; Allison T. Yip ; Alison V. Thach ; April R. Rodriguez ; Timothy J. Deming ; Daniel T. Kamei ; ^{kamei@seas.ucla.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：N-hydroxysuccinimide (PubChem CID ; 80170) ; 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (PubChem CID ; 15908) ; Tetrahydrofuran (PubChem CID ; 8028) ; Ammonium sulfate (PubChem CID ; 6097028) ; Dimethyl sulfoxide (PubChem CID ; 679)
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：30 December 2015
• 年：2015
• 卷：496
• 期：2
• 页码：903-911
• 全文大小：1528 K

文摘

We previously investigated the intracellular trafficking properties of our novel poly(l-glutamate)₆₀-b-poly(l-leucine)₂₀ (E₆₀L₂₀) vesicles (EL vesicles) conjugated to transferrin (Tf). In this study, we expand upon our previous work by investigating the drug encapsulation, release, and efficacy properties of our novel EL vesicles for the first time. After polyethylene glycol (PEG) was conjugated to the vesicles for steric stability, doxorubicin (DOX) was successfully encapsulated in the vesicles using a modified pH-ammonium sulfate gradient method. Tf was subsequently conjugated to the vesicles to provide active targeting to cancer cells and a mode of internalization into the cells. These Tf-conjugated, DOX-loaded, PEGylated EL (Tf-DPEL) vesicles exhibited colloidal stability and were within the allowable size range for passive and active targeting. A mathematical model was then derived to predict drug release from the Tf-DPEL vesicles by considering diffusive and convective mass transfer of DOX. Our mathematical model reasonably predicted our experimentally measured release profile with no fitted parameters, suggesting that the model could be used in the future to manipulate drug carrier properties to alter drug release profiles. Finally, an in vitro cytotoxicity assay was used to demonstrate that the Tf-DPEL vesicles exhibited enhanced drug carrier efficacy in comparison to its non-targeted counterpart.